Physicochemical Properties
| CAS # | 2730151-31-0 |
| Appearance | Typically exists as solid at room temperature |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | PI3Kδ/γ-IN-3 (compound 58) exhibited antiproliferative efficacy against DLBCL (B-cell lymphoma) cells after 72 hours [1]. SUDHL-6 and DOHH2 cells have their cell cycles stopped in the G0/G1 phase by PI3Kδ/γ-IN-3 (0.5 μM, 24 h) [1]. In SUDHL-6 and DOHH2 cells, PI3Kδ/γ-IN-3 (1.5 and 2 μM, 48 hours) causes apoptosis [1]. |
| ln Vivo | PI3Kδ/γ-IN-3 (Compound 58) decreased tumor volume in mice in a dose-dependent manner without showing signs of toxicity when given orally, once daily, for 14 days at 5 and 10 mg/kg [1]. |
| Cell Assay |
Cell proliferation assay[1] Cell Types: SUDHL-4, SUDHL-6 and DOHH2 Cell Tested Concentrations: Incubation Duration: 72 hrs (hours) Experimental Results: demonstrated anti-proliferative activity against SUDHL-4 with IC50 of 0.03 ± 0.03, 0.06 ± 0.01 and 0.20 respectively ± 0.04 μM , SUDHL-6 and DOHH2 cells, respectively. Cell cycle analysis[1] Cell Types: SUDHL-6 and DOHH2 Cell Tested Concentrations: 0.5 μM Incubation Duration: 24 hrs (hours) alone or in combination with Ibrutininb (0.5 μM or 1 μM) Experimental Results: Causes loss of cells in G2/M phase and leads to G2 /M phase cell loss. The percentage of cells in G0/G1 phase increases. Cell cycle arrest was induced in both cells alone or in combination with ibrutinib. Apoptosis analysis[1] Cell Types: SUDHL-6 and DOHH2 Cell Tested Concentrations: 1.5 μM and 2 μM Incubation Duration: 48 hrs (hours) alone or in combination with Ibrutininb (1.5 μM or 1 μM) Experimental Results: Demonstrated induction of cells in both SUDHL Apoptosis-6 and DOHH2 cells, and the combination was stronger than treated alone. |
| Animal Protocol |
Animal/Disease Models: SD rat[1] Doses: 5 mg/kg Route of Administration: Oral or intravenous (iv) (iv)administration (pharmacokinetic/PK/PK analysis) Experimental Results: PI3Kδ/γ-IN-3 (compound PK curve of 58) Compound dose (mg/kg) Route of administration Cmax (ng/mL) Tmax (h) AUC0-t (h·μg/L) T1/2 (h) CL (L/h/kg) Vss (L/kg) F (%) 58 5 Oral 3637.81 3.33 8612.57 9.46 0.79 -- 126.5 5 intravenous (iv) (iv)injection 860.09 0.08 6806.92 2.79 0.75 2.86 -- PK curve: Cmax, maximum plasma concentration; maximum time, Tim |
| References | [1]. Liu K, et al. Discovery, Optimization, and Evaluation of Potent and Selective PI3Kδ-γ Dual Inhibitors for the Treatment of B-cell Malignancies. J Med Chem. 2022 Jul 13. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |